Santiago Celine, Labrador Juan-Pablo, Bashaw Greg J
Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland.
Cell Rep. 2014 Apr 10;7(1):153-65. doi: 10.1016/j.celrep.2014.02.037. Epub 2014 Mar 27.
Transcription factors establish neural diversity and wiring specificity; however, how they orchestrate changes in cell morphology remains poorly understood. The Drosophila Roundabout (Robo) receptors regulate connectivity in the CNS, but how their precise expression domains are established is unknown. Here, we show that the homeodomain transcription factor Hb9 acts upstream of Robo2 and Robo3 to regulate axon guidance in the Drosophila embryo. In ventrally projecting motor neurons, hb9 is required for robo2 expression, and restoring Robo2 activity in hb9 mutants rescues motor axon defects. Hb9 requires its conserved repressor domain and functions in parallel with Nkx6 to regulate robo2. Moreover, hb9 can regulate the medio-lateral position of axons through robo2 and robo3, and restoring robo3 expression in hb9 mutants rescues the lateral position defects of a subset of neurons. Altogether, these data identify Robo2 and Robo3 as key effectors of Hb9 in regulating nervous system development.
转录因子决定了神经多样性和布线特异性；然而，它们如何协调细胞形态的变化仍知之甚少。果蝇的Roundabout（Robo）受体调节中枢神经系统中的连接性，但其精确表达域是如何建立的尚不清楚。在这里，我们表明同源结构域转录因子Hb9在Robo2和Robo3的上游起作用，以调节果蝇胚胎中的轴突导向。在腹侧投射的运动神经元中，hb9是robo2表达所必需的，并且在hb9突变体中恢复Robo2活性可挽救运动轴突缺陷。Hb9需要其保守的抑制域，并与Nkx6并行发挥作用来调节robo2。此外，hb9可以通过robo2和robo3调节轴突的中外侧位置，并且在hb9突变体中恢复robo3表达可挽救一部分神经元的外侧位置缺陷。总之，这些数据确定Robo2和Robo3是Hb9在调节神经系统发育中的关键效应因子。
